title: Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.
abstract: Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm. nih.gov:80/htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP.
authors.affiliation: Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Burns and Allen Cedars-Sinai Research Institute, Los Angeles, CA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Briggs
authors.forename: G R
authors.initials: GR
authors.lastname: Mortier
authors.forename: W G
authors.initials: WG
authors.lastname: Cole
authors.forename: L M
authors.initials: LM
authors.lastname: King
authors.forename: S S
authors.initials: SS
authors.lastname: Golik
authors.forename: J
authors.initials: J
authors.lastname: Bonaventure
authors.forename: L
authors.initials: L
authors.lastname: Nuytinck
authors.forename: A
authors.initials: A
authors.lastname: De Paepe
authors.forename: J G
authors.initials: JG
authors.lastname: Leroy
authors.forename: L
authors.initials: L
authors.lastname: Biesecker
authors.forename: M
authors.initials: M
authors.lastname: Lipson
authors.forename: W R
authors.initials: WR
authors.lastname: Wilcox
authors.forename: R S
authors.initials: RS
authors.lastname: Lachman
authors.forename: D L
authors.initials: DL
authors.lastname: Rimoin
authors.forename: R G
authors.initials: RG
authors.lastname: Knowlton
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
mesh_terms: D000130:Achondroplasia / Q000145:classification / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002356:Cartilage; D064236:Cartilage Oligomeric Matrix Protein; D002648:Child; D003062:Codon; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D005260:Female; D005799:Genes, Dominant; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D064235:Matrilin Proteins; D010009:Osteochondrodysplasias / Q000145:classification / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D003062:Codon; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human